DENVER, R.J.: Evolution of the Corticotropin-Releasing Hormone Signaling System and its Role in Stress-Induced Developmental Plasticity

Post-embryonic development can be strongly influenced by the external environment. Amphibian tadpoles show strong responses to environmental signals, exhibiting continuous variation in the timing of metamorphosis. The most important environmental variable for a tadpole is water availability. We analyzed the ecological and physiological bases for the timing of metamorphosis in tadpoles exposed to habitat desiccation. Tadpoles of several species have been shown to accelerate metamorphosis when their ponds dry. Our ecological studies suggest that tadpoles use special senses to detect deleterious changes in their larval habitat. Habitat desiccation results in the precocious activation of the thyroid and the interrenal axes, the hormones of which drive metamorphosis. Several lines of evidence suggest that a common neuroendocrine signaling pathway involving the stress neuropeptide corticotropin-releasing hormone (CRH) determines the activation of the two systems. A role for CRH in regulating the pituitary-thyroid axis in addition to the pituitary-adrenal (interrenal) axis has been demonstrated in representatives of all vertebrate classes except mammals. The CRH signal is transduced by at least two receptor subtypes and may be modulated by a secreted binding protein. Taken together with ecological findings, our data suggest that tadpoles can respond adaptively to environmental deterioration by mounting a classical neuroendocrine stress response. Evolutionary conservation of the role of CRH in mediating developmental plasticity is suggested by recent demonstrations in mammals that CRH of fetal and/or placental origin determines the length of the gestational period and may be involved with precipitating preterm birth. (supported by NSF grant IBN9974672)